Heart Views

: 2023  |  Volume : 24  |  Issue : 2  |  Page : 67--92

2022 Saudi guidelines for the management of dyslipidemia

Jamilah AlRahimi1, Shukri AlSaif2, Mirvat Alasnag3, Zuhier Awan4, Fawaz Almutairi5, Hajer Al Mudaiheem6, Baris Gencer7, Alberico L Catapano8, François Mach9, Adel Tash10,  
1 Department of Cardiology, King Faisal Cardiac Center, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Sciences, Dammam, Saudi Arabia
2 Department of Cardiology, Saud AlBabtain Cardiac Center, Dammam, Saudi Arabia
3 Department of Cardiology, Catheterization Laboratory, King Fahd Armed Forces Hospital, Jeddah, Saudi Arabia
4 Medicine, Biochemistry and Molecular Genetics, Clinical Biochemistry Department, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
5 Department of Cardiology, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia
6 Therapeutic Affairs Department, Ministry of Health, Riyadh, Saudi Arabia
7 Department of Cardiology, Geneva University Hospital, Geneva; Institute of Primary Healthcare (BIHAM), Bern University, Bern, Switzerland
8 Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy
9 Department of Cardiology, Geneva University Hospital, Geneva, Switzerland
10 Cardiac Services Development, Ministry of Health; National Heart Center, Saudi Health Council, Riyadh, Saudi Arabia

Correspondence Address:
Dr. Jamilah AlRahimi
King Abdullah International Medical Research Center, College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, P.O. Box 9515, Jeddah 21423
Saudi Arabia

How to cite this article:
AlRahimi J, AlSaif S, Alasnag M, Awan Z, Almutairi F, Al Mudaiheem H, Gencer B, Catapano AL, Mach F, Tash A. 2022 Saudi guidelines for the management of dyslipidemia.Heart Views 2023;24:67-92

How to cite this URL:
AlRahimi J, AlSaif S, Alasnag M, Awan Z, Almutairi F, Al Mudaiheem H, Gencer B, Catapano AL, Mach F, Tash A. 2022 Saudi guidelines for the management of dyslipidemia. Heart Views [serial online] 2023 [cited 2023 Sep 22 ];24:67-92
Available from: https://www.heartviews.org/text.asp?2023/24/2/67/372458

Full Text


Since its establishment in 2014, the Saudi Health Council (SHC) has stepped up to embrace a core mission of “establishing regulations that ensure coordination and integration among health stakeholders to improve health care in Saudi Arabia, and to be an inspirational reference to a world-class Saudi health system.” In light of this mission, SHC took over the responsibility to put forward efficient health-care strategies, regulations, and policies in the kingdom to ensure that hospitals run by the Ministry of Health (MOH) and other government agencies are operated in adherence to the principles of economic management as well as performance and quality standards.

In light of the alarming status of atherosclerotic cardiovascular disease (ASCVD), risk factors in Saudi Arabia and recent data about serious gaps in the quality of health-care delivery, specifically in areas of clinical effectiveness, patient-centered care, and patient safety,[1],[2] SHC has taken the worrying status of dyslipidemia in Saudi patients very seriously and assigned a task force to develop national guidelines for dyslipidemia management to be a cornerstone for the development of subsequent guidelines addressing other ASCVD risk factors among the Saudi population.


The current recommendations state that adherence to lifestyle modifications and the use of lipid-lowering medications are the cornerstones for reducing the risk for ASCVD in patients with dyslipidemia. Nonetheless, the management of dyslipidemia has undergone a number of significant changes over recent years, leading to revisions in both European and US guidelines.[3],[4] Such revisions include new thresholds and goals, changes in primary and secondary preventive approaches, the new classification of the risk-enhancing factors, and new definitions for risk groups; these changes are also influenced by new equation values, recommendations, and actions.[3],[4],[5] However, the published international guideline cannot be directly applied to the Saudi population who differs in a number of aspects from European and American populations.[6]

In Saudi Arabia, the mean age of the population is younger, with 72.5% aged between 15 and 64 years. The Saudi population is multiethnic, and disparities between groups are prevalent due also to geographical and cultural factors. The annual growth rate of the Saudi population is 2.3%, with a median life expectancy of 75 years. There is a high prevalence of obesity (24.7%), and approximately 25.2% of the total population have diabetes mellitus (DM). In addition, there is a lack of primary health-care units (0.6 PHC per 10,000 population).[7],[8],[9],[10] In Saudi Arabia, over the past years, ischemic heart disease has persisted in ranking first as the top cause of death from 2000 to 2019, followed by stroke.[11] Furthermore, cardiovascular diseases (CVDs) collectively remained as the leading cause of disability-adjusted life years (DALYs quantifies the health loss due to specific diseases and injuries[150]) in Saudi Arabia from 1990 to 2017 [Figure 1].[12] The prevalence of ASCVD risk factors has been consistently high over the past decades, and multiple surveys have shown the continued high prevalence of dyslipidemia, unhealthy diet, hypertension, smoking, obesity, physical inactivity, and diabetes in Saudi Arabia across different age groups.[7],[8],[13],[14],[15],[16]{Figure 1}

These Saudi clinical practice guidelines provide recommendations applicable to Saudi patients with or at risk of developing CVD. The guidelines summarize and evaluate available evidence with a focus on the Saudi published literature and the best available up-to-date research evidence from other international research and guidelines. It is worth emphasizing that the European Society of Cardiology Guideline recommendations, categorizations, targets, and cutoffs were the main guide while developing these Saudi dyslipidemia guidelines since it is strongly believed that the tighter control imposed by the European Society of Cardiology is the most appropriate to be implemented in Saudi Arabia given our population's biochemistry.


Consensus approach

The task force recruited Saudi experts and specialists from different regions of the kingdom, including the Director General of the National Heart Center and other members representing various health sectors, to typify professionals involved with managing patients with dyslipidemia. One member representing the Drug Policy and Regulation at the Saudi MOH ensured all recommendations are in line with the health economic considerations that consider both clinical-and cost-effectiveness perspectives. In addition to European experts who extensively reviewed the guidelines as well as the endorsement process. Members of the assigned task force have volunteered their time and effort to produce these recommendations with the highest level of proficiency.


In this document, the Saudi experts have provided recommendations and guidance for detailed risk assessment, the position of newer cholesterol-lowering drugs within the management algorithm, and the need for special attention to patient subgroups. Besides, the experts recommended treatment algorithms using an evidence-based approach. The guideline updated the patient risk assessment and treatment options in primary and secondary prevention using the most up-to-date evidence to inform the clinicians during the process of shared decision-making, aiming to align these decisions with the recent recommendations of the international guidelines. This document has been developed for health-care professionals to facilitate informed communication with individuals about their cardiovascular (CV) risk and the benefits of adopting and sustaining a healthy lifestyle and early modification of their lipid-related CV risk. This guideline has the potential to promote up-to-date management strategies and to translate them into locally delivered health-care services, in line with the recommendations of the World Health Organization (WHO).[6]

Literature review

A literature search was made in English language to identify published articles related to ASCVD and or lipids related to Saudi, Gulf, or Arab populations. Where local data or published material was found, it was always used. The designated steering committee also reviewed the previously published international guidelines and related statements deemed pertinent to these guidelines; thus, obviating the need to implement existing guideline recommendations of different regions.

Different authors had the responsibility to research specific sections of the guidelines and produce a draft that was discussed in a series of virtual meetings. During these meetings, different recommendations were considered and a consensus was reached, or voting was made on the adoption for each recommendation based on the strength of available evidence for that recommendation and its applicability to practice conditions within Saudi Arabia. The level of evidence and the strength of the recommendation are adapted from the 2019 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) Guidelines for the management of dyslipidemia,[3] where management options were graded as per predefined scales [Table 1]. {Table 1}

A third party coordinated the preparation of these new guidelines and provided professional writing and editorial support. After appropriate revisions, the final document was approved by all task force members.

The overall aim of the present document is, therefore, to provide a nationwide, evidence-based policy, and guidelines to implement a unified approach for the management of dyslipidemia in Saudi Arabia.

All experts involved in the development of these guidelines declared no real or potential sources of conflicts of interest.

 Cardiovascular Disease Risk and Risk Groups

Total cardiovascular risk estimation

CV risk is the likelihood of a person to develop an atherosclerotic CV event over a defined period of time, and the total risk of developing CVD, i.e. total CV risk estimation, is determined by the combined effect of multiple risk factors which commonly coexist and act multiplicatively.[3] Risk assessment systems are used to improve management decisions by way of providing a 10-year estimate of an individual's risk for ASCVD events, and therefore, many systems have been developed and comprehensively reviewed.[17],[18],[19],[20],[21],[22],[23],[24],[25],[26] Ideally, risk charts should be based on country-specific cohort data since estimating risk based on cohorts that differ greatly from the target population could jeopardize the benefit of risk charts in practical terms. However, these are not available for most countries, including Saudi Arabia.[27],[28]

A recent expert opinion was published in 2018 by Alshamiri et al.,[28] in which an expert panel had convened to review the commonly used international guidelines in Asia and the Middle East and to determine their applicability in the region. There was agreement that existing risk calculators may not be suitable for Asia and the Middle East, with many concerns about the validity of these calculators in local populations. However, despite disparities on which risk calculator to use across the countries represented, the panel advocated the value of using such tools to assess CV risk. In fact, the Systematic Coronary Risk Estimation (SCORE) system[29],[30] is the most adopted in Saudi Arabia despite not being yet validated for the Saudi population. It provides a relatively straightforward method and allows for recalibration for use in different populations. However, it estimates the risk of fatal CVD events only and overlooks the total CVD events which occur at a higher frequency (approximately 3-to 4-fold greater).[28],[31],[32] Thus, the development of a new risk calculator that is optimized for the Saudi population, and that includes important risk factors in terms of relevance to the Saudi community (including nontraditional risk factors), is a gap that needs to be met to ensure all patients are adequately assessed and managed.

Recommendations for CVD risk estimation in Saudi Arabia are presented in [Table 2].{Table 2}

In this context, it should be recalled that the mean age of presentation with acute coronary syndrome (ACS) in Saudi Arabia is almost 10 years younger than the average age in developed countries, and this is due to the high prevalence of poorly controlled ASCVD risk factors.[33],[34] Thus, risk factor screening in Saudi Arabia, including the lipid profile, should be considered earlier than recommended in developed countries [Table 2].

Risk categories

The cutoff points used to define different risk categories in the 2019 ESC and EAS guidelines for the management of dyslipidemias[3] are recommended to be adopted in Saudi Arabia and are presented in [Table 3]. From a practical point, individuals with certain conditions (such as patients with documented CVD, older individuals with long-standing DM, chronic kidney disease (CKD), familial hypercholesterolemia (FH), and extreme lipoprotein (a) (Lp [a]) elevation, coronary artery calcium (CAC) score >100, or carotid or femoral plaques) are at high or very high risk of CVD.{Table 3}

Treatment goals across total cardiovascular disease risk categories

Treatment goals have been defined in accordance with an overall ASCVD risk score determining the 10-year risk of any CV event.[3] In general, it is accepted that the reduction in low-density lipoprotein cholesterol (LDL-C) levels should persist indefinitely as the reduction is associated with a parallel reduction of ASCVD events. The evidence has not identified a predetermined level of LDL-C below which benefit ceases or harm supersedes. The purpose of defining targets is to attain maximum compliance with lipid-lowering management on the part of both the patients and practitioners. As such, it is reasonable to target an LDL-C level that is as low as possible.[37],[38],[39] However, individual variations in response to therapy have been reported with ample evidence of residual risk. It is, therefore, imperative to individualize the treatment strategy.[40] Treatment goals across total CVD risk categories are presented in [Figure 2].{Figure 2}

Patients with FH are at high CV risk, and the treatment goal is LDL cholesterol <1.8 mmol/l or at least a 50% reduction in LDL cholesterol. However, early detection and prevention of events are the real goals in the management of this high-risk population.

Risk factors

The risk factors for ASCVD are age, gender, cholesterol and lipoprotein abnormalities, hypertension, DM, prediabetes, insulin resistance, and lifestyle factors (including tobacco use, overweight and obesity, unhealthy diet, limited physical activity, and air pollution) [Figure 3].[4],[35],[41] Continuing exposure to risk factors results in further ASCVD progression. Total CVD risk depends on the individual's overall risk factor profile [Table 4], [Table 5], [Table 6].{Figure 3}{Table 4}{Table 5}{Table 6}

Age and gender

Age and gender are the main drivers of CVD risk. Women >75 and men >65 years of age are almost always at high 10-year CVD risk.[41] In Saudi Arabia, results from a cross-sectional community-based study covering the whole population from all the 20 health regions of the kingdom aged between 15 and 64 years revealed that triglycerides (TGs) and the ratio of total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C) were significantly higher in males, while HDL-C and TC were significantly higher in females. No significant differences in LDL-C concentration according to gender were observed (P = 0.341). Moreover, significantly higher dyslipidemia prevalence of TC and TG was found in older subjects[42] [Supplementary Table 1].[INLINE:1]

Low-density lipoprotein cholesterol

LDL-C is highly atherogenic, and the cumulative LDL-C arterial burden is a central determinant for ASCVD initiation and progression. Lowering LDL-C reduces the risk of CV events, and both relative and absolute risk reductions are associated with the magnitude of LDL-C reduction.[43] Assessment of LDL-C is the mainstay component of the management of ASCVD risk.[3],[44] Alike, the relationship between nonhigh-density lipoprotein cholesterol (non-HDL-C), which encompasses all atherogenic, i.e. Apo-B-containing lipoproteins; and CV risk is at least as strong as the relationship with LDL-C.[41] Apo-B-containing lipoproteins have a central causal role in the initiation and progression of atherosclerosis, and quantitation of Apo-B directly estimates the number of atherogenic particles in plasma.[3] In Saudi Arabia, dyslipidemia is the most prevalent ASCVD risk factor (68.6%),[45] and the prevalent pattern is low HDL-C and high TGs which is different from many other regions in the world. The high prevalence of metabolic syndrome, DM, FH, and consanguineous marriages is the main contributing factor behind this pattern in the kingdom.[46],[47]


With regard to hypertension, a national survey conducted in the kingdom including 10,735 participants found that 15.2% (17.8% for males and 12.5% for females) and 40.6% were hypertensive or borderline hypertensive, respectively.[48] DM is steadily increasing and rapidly becoming one of the main health issues in Saudi Arabia, with major fear about millions of undiagnosed cases.[49] More than one quarter (25.2%) of the Saudi adult population has diabetes, which is predicted to more than double by 2030. Moreover, the WHO ranks Saudi Arabia second in the prevalence of DM in the Middle East region and seventh in the world.[50] In fact, Saudi Arabia reached a point where DM is considered an epidemic.[51] Atherogenic dyslipidemia is one of the major risk factors for CVD in people with type 2 DM (of which about 50% have elevated TGs or low HDL-C levels) and in people with abdominal obesity and insulin resistance or impaired glucose tolerance.[3]


Cigarette smoking prevalence in Saudi Arabia has shown to be more prevalent in the Northern regions, relatively high in the male population at 32.5%, in particular among those aged between 25 and 44 years old, and 3.9% among females.[52] Heart disease, DM, and hypertension were already present and diagnosed in 5.2%, 12.5%, and 23.2%, respectively, among smokers surveyed in that study. Ibrahim Alasqah et al.[53] reported a prevalence of smoking ranging from 12.7% to 39.6% among adolescents regardless of their educational stage. The prevalence among female adolescents ranged between 1.6% and 11.1%.[54] Moreover, epidemiological data have shown alarming evidence of high water pipe usage among Saudi teenagers and college students.[55]

Overweight and obesity

The prevalence of overweight and obesity in the Saudi population across different age groups is high, indicating ineffectiveness or lack of preventive measures [Figure 4].[8] According to World Atlas data, Saudi Arabia is ranked 12 among obese countries.[56] The Global Burden of Metabolic Risk Factors for Chronic Diseases Collaboration revealed that both overweight (body mass index (BMI) ≥25 to <30 kg/m2) and obesity (BMI ≥30 kg/m2) were associated with a significantly increased risk of coronary heart disease (CHD) and stroke, compared with normal weight (BMI ≥20 to <25 kg/m2), with 50% of the excess risk of overweight and 44% of the excess risk of obesity for CHD mediated by blood pressure (BP), cholesterol, and glucose.[57]{Figure 4}

Consumption of caffeinated or carbonated drinks

Excessive consumption of caffeinated or carbonated drinks all sweetened with sugar, higher consumption of foods rich in fat, carbohydrates, and salt, and lower consumption of fruits and vegetables among the Saudi population are associated with an increased risk of dyslipidemia.[58] Moradi-Lakeh et al. conducted a household survey in 2013 of 10,735 Saudi individuals aged ≥15 years. Dietary guideline recommendations were met by only 5.2% of individuals for fruits, 7.5% for vegetables, 31.4% for nuts, and 44.7% for fish.[59] The majority of Saudis are not active enough to meet the recommended guidelines for moderate-to-vigorous physical activity.[60] Females were significantly less active than males in terms of percentages spent more than 1680 metabolic equivalent values (METs [physical activities were assigned MET values based on the compendium of physical activity[151] and the compendium of physical activity for youth[152].])-min/week (=60 min per day × 7 days/week × 4 METs [moderate-intensity physical activity]) and more than 2520 METs-min/week (=60 min per day × 7 days/week × 6 METs [moderate-to-vigorous-intensity physical activity]) (21.9% vs. 55.5%, and 12.9% vs. 43.5% for Saudi females and males, respectively, P < 0.01).[61] The prevalence of physical inactivity appears to increase with advancing age. The most important barriers to physical inactivity are the lack of time, followed by lack of appropriate places (especially for females), and lack of facilities and resources. Physical inactivity is significantly associated with obesity and waist circumference in adults, children, and adolescents.[60]

Air pollution

Air pollution is a major contributor to the global burden of disease, and accounted for 12% and 20% of all deaths and CVD deaths, respectively, in 2019. Further, air pollution was the 4th highest-ranking risk factor for mortality, with more attributable deaths than high LDL-C, high BMI, physical inactivity, or alcohol use.[62] Air pollution is a complex and dynamic mixture of numerous compounds in gaseous and particle form, originating from diverse sources. Particulate matter is responsible for the vast majority of the disease burden through its impact on ischemic heart disease and stroke.[63],[64] In Saudi Arabia, several studies have emphasized the association between air pollutants and CVD, as well as the detrimental induction of genes involved in inflammation, lipid metabolism, and atherosclerosis[65],[66] [Supplementary Table 1].

Risk enhancers

Risk-enhancing factors are independent of other risks associated with ASCVD. Assessing for risk-enhancing factors can help guide decisions about preventive interventions in adults at borderline or intermediate risk and to adjust the intensity of LDL-lowering therapy [Table 7].[4],[35] Family history of premature ASCVD (males, age <55 years and females, age <60 years) is a risk-enhancing factor that should be considered for clinician–patient risk discussion [[Table 8]; Recommendations for FH management in Saudi Arabia]. Metabolic syndrome, another risk enhancer, is characterized by the clustering of central obesity, dyslipidemia, elevated BP, and hyperglycemia.[35] A large cross-sectional study that included 12,126 Saudi subjects reported a high prevalence of metabolic syndrome in Saudi Arabia that equals 39.8% (34.4% in men and 29.2% in women). The most frequently observed component of metabolic syndrome was low levels of HDL-C, followed by abdominal obesity.[79] Despite patients with metabolic syndrome being classified as high-risk, precise figures about its prevalence and response to treatment in Saudi Arabia are still lacking.[80]{Table 7}{Table 8}

CKD is an important disorder worldwide that affects more than 10% of adults and increases the risk of many adverse outcomes; among them, CVD is particularly important. As CKD progresses, kidney-specific risk factors for CV events and disease come into play and ultimately increase the risk for CVD. Moreover, raised concentrations of albumin in urine and impaired kidney function increase the risk of CVD by 2 to 4 times. CVD is the leading cause of death in persons with CKD.[81],[82] In Saudi Arabia, adequate epidemiological data about CKD is lacking. However, figures from a pilot community-based screening program in 2010 concluded that the prevalence of CKD is around 5.7% in Riyadh city.[83]

Risk modifiers

Risk modifiers are additional risk factors or individual information that can modify the calculated risk. Assessment of risk modifiers is particularly relevant if the individual's risk is close to a decision threshold (i.e. in low-risk or very high-risk situations, additional information is less likely to alter management decisions) [Table 8].[41]

COVID-19 and cardiovascular disease

The CV complications of acute coronavirus disease 2019 (COVID-19) are well reported in several studies.[90],[91],[92],[93],[94] A recent study by Xie et al.[95] used databases of 153,760 individuals with COVID-19 infection, 5,637,647 individuals as contemporary controls, and 5,859,411 individuals as historical controls to estimate risks and 1-year burdens of CV outcomes. The results revealed that individuals with COVID-19 are at increased risk of incident CV disease categories including ischemic and nonischemic heart disease, myocarditis, pericarditis, dysrhythmias, heart failure, thromboembolic disease, and cerebrovascular disorders beyond the first 30 days after infection. These risks were evident among all individuals, whether hospitalized or not during the acute phase of the COVID-19 infection. These results flagged the evidence that CV disease risk and 1-year burden in survivors of acute COVID-19 are substantial, and care of those survivors should include attention to CV disease.

 Management of Dyslipidemia in Different Clinical Settings

Aggressive lipid management has been demonstrated to improve CV outcomes in specific clinical settings such as ACS and other very high-risk entities, namely diabetes, CKD, and FH [Table 9].{Table 9}

Acute coronary syndromes

With respect to ACS, intensive statin therapy early after a clinical event can reduce future events permitting a significant early pleiotropic effect. Randomized evidence has unequivocally demonstrated the benefit with early initiation of treatment, that is, in-hospital and continued long-term.[96],[97],[98],[99] Furthermore, high-intensity statin therapy in all patients with ACS is recommended irrespective of the baseline LDL-C values. Immediately after an ACS, it is well known that LDL levels will drop; therefore, ideally, assays should be drawn within the first 24 h.[100] Assays before the event are more reliable. The recommended target for LDL-C is a 50% reduction and a level of <1.4 mmol/L (<55 mg/dL). For individuals suffering recurrent events (even in a different territory) within 2 years, a goal of <1.0 mmol/L (<40 mg/dL) for LDL-C is recommended. For very high-risk patients, the first-line treatment strategy is recommended to include high-intensity statin in combination with ezetimibe. If the target is not reached, the addition of proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies is recommended. For extremely high-risk (extremely high risk = post-ACS + history of other vascular event/peripheral artery disease/polyvascular disease/multivessel coronary artery disease/familial hypercholesterolemia) patients, initiation of triple combination therapy should be considered the first-line approach.[5],[74],[77],[101] These agents achieve a sustained reduction in all subgroups and permit a reduction in all events, including cerebrovascular, rehospitalizations, and all-cause death.

Diabetes mellitus

DM is often referred to as an ASCVD equivalent. It confers an independent risk for multiple CV disorders that is double other factors.[102] Fasting blood glucose has a log-linear correlation with the risk of vascular disease at all concentrations, including below 7 mmol/L, i.e. below the threshold for diabetes. Those with end-organ damage, such as retinopathy and nephropathy, and microvascular dysfunction have a higher risk of CV events. Additional risk factors render diabetics at an even higher risk of CV events. Diabetics with concomitant coronary artery disease have a significantly worse prognosis and survival after an ACS.[103] Optimal dosing, escalation, and lipid management are critical. Although data suggests a higher risk of development of new-onset diabetes with statin therapy, the majority occur in the subset with prediabetes. The magnitude of the absolute reduction of LDL-C levels and, consequently CV events, suggest intensive therapy should be encouraged and outweighs any potential risk of new-onset diabetes.[104],[105],[106]

Of note, data extracted from the Odyssey and Fourier studies revealed no increase in the risk of new-onset diabetes with the use of PCSK9 monoclonal antibodies.[76],[77] In their meta-analysis, de Carvalho et al. reported an increase in fasting blood glucose and glycated hemoglobin (HbA1c) levels in 68,123 patients who were taking concomitant statins and PCSK9 monoclonal antibodies; however, this did not result in a higher incidence of type 2 diabetes. Furthermore, the analysis only included short-term follow-up. The subanalysis of the landmark Odyssey trial did not observe conversion to diabetes with these agents.[77],[107]

Chronic kidney disease

CKD stage 3 is considered high, and stage 4–5 is considered very high risk. An estimated glomerular filtration rate of <60 mL/min/1.73 m2 and an albumin creatinine ration of 1.1 mg/mmol (10 mg/g) or more are independent predictors of mortality. Therefore, a high-intensity statin is recommended in those with adjunctive risk, established ASCVD, or presenting with an ACS to achieve the maximum reduction.[82] Although adverse events with statin therapy require monitoring, appropriate intensity is advisable as this population has an overall higher risk of CV events in patients with CKD.[108] In addition, in patients with CKD presenting with ACSs, PCSK9 monoclonal antibodies were associated with a lower incidence of ASCVD events and all-cause death across all ranges of dysfunction. In fact, the absolute reduction in the major adverse CV events (MACE) with PCSK9 monoclonal antibodies is greater with more advanced CKD. This further supports the need to intensify lipid-lowering therapy and consider combination regimens early.[109],[110],[111]


Women have historically been underrepresented in prevention trials. However, meta-analyses and pooled data for both statin and nonstatin therapy showed an equivalent benefit of women and men in preventive therapies.[68],[101],[112] Lipid-lowering agents are not recommended during pregnancy or lactation due to the absence of evidence suggesting benefit or harm. However, women with pregnancy-related complications, including gestational diabetes, preeclampsia, eclampsia, and a miscarriage, are at higher overall CV risk.[113],[114] Therefore, risk assessment and lipid-lowering measures should be appropriately timed in women after delivery.

Familial hypercholesterolemia

Dyslipidemia has long been recognized to have a strong genetic basis, which is explicitly related to abnormal lipoproteins levels. When this becomes in its more extreme forms, it can be manifested as familial dyslipidemias. There are different types of familial lipid disorders; among these, FH is the prototypical form of genetic dyslipidemia [Supplementary Table 2].[3],[116],[117][INLINE:2]

FH is an autosomal codominant genetic disorder where both homozygous and heterozygous forms are characterized by elevations in LDL-C >95th percentile for age and sex. This disorder represents a high-risk population where adequate research on the prevalence and response to treatment in Saudi Arabia is lacking. Nevertheless, it remains underdiagnosed and undertreated in the region, with an estimated prevalence of 1/232 based on the Gulf FH Registry. In addition to elevated LDL-C, patients with FH often present with premature ASCVD. Despite the diagnosis of high levels of LDL-C, and even after documented CV events, FH frequently remains undetected and underdiagnosed in the entire Gulf region.[118] Early diagnosis and aggressive therapy are necessary to delay ASCVD complications and reduce future events.

Limited data are available worldwide about FH prevalence, and various studies revealed that FH is underdiagnosed, with only 1% are identified in most countries.[119] In 2021, the results of a multicenter, multinational Gulf FH registry[118] included adults (≥18 years old; 3713 patients had suspected FH and 306 patients had definite or probable FH) recruited from five Arabian Gulf countries over a 5-year period revealed a higher prevalence of FH in the Arabian Gulf region (0.9%; 1:112) compared to the global figures (about 3-fold). Consanguinity, first cousin marriage, and endogamy rates in Arabian countries are among the highest in the world and are believed to be the major factors contributing to the high prevalence of FH.[120] These worrying figures impose a “call-to-action” for further confirmation studies in Saudi Arabia, in addition to the urgent need for implementation of a nationwide screening program, raising FH awareness, and improving FH management strategies.[118],[121] Patients require intensive treatment with statins and ezetimibe and/or colesevelam. PCSK9 inhibitors have been approved for their management. Recommendations for FH management in Saudi Arabia are presented in [Table 10].{Table 10}

 Regimen Selection

Pharmacological interventions

Pharmacological interventions and approved indications

When lifestyle interventions are insufficient to attenuate the risk of atherosclerotic vascular disease, drug treatment becomes an essential part of the overall management. Lipid modifying drugs, in addition to continuing lifestyle interventions, should be considered for individualized patient regimen selection. The treatment goals include serum LDL-C, serum TGs or non-HDL-C and Lp(a) [Table 11] and [Table 12].{Table 11}{Table 12}

Regimen selection for different clinical settings

Individuals who have developed ASCVD, DM, or CKD do not require any further risk estimation. These individuals are at very high risk, and pharmacological intervention is recommended to reduce their risk to the lowest possible in addition to appropriate lifestyle interventions. Others require an assessment of overall ASCVD risk. Therapy is recommended for subjects with FH or those that have an elevated 10-year atherosclerotic vascular risk.

Statins are the initial drugs of choice for all patients being considered for pharmacological interventions. The selection of the individual statin must be based on the level of risk and the level of baseline LDL-C. Moderate-intensity statins are expected to lower LDL-C between 30% and 50%, while high-intensity statins could reduce this by more than 50%. Patients who do not achieve the desired target should have combination therapy. Patients with FH are likely to require combination therapy with a high-intensity statin, a cholesterol absorption inhibitor ezetimibe, and either PCSK9 monoclonal antibody or inclisiran. Patients that have TGs 135 mg/dL or higher up to 500 mg/dL despite initial therapy with statins should be considered for combination therapy with eicosapentaenoic acid ethyl ester, which has been shown to reduce the risk of ischemic events, including CV death.[122] Patients admitted with ACS are at particularly high risk for recurrent events and justify in-hospital initiation of lipid-lowering therapy starting with high-intensity statin upon admission.[123] Patients with DM must be treated in the same way as patients with established ASCVD. Many of these patients also have elevated TGs that may be related to poor diabetic control. Therefore, these patients require optimization of diabetic control in addition to lifestyle interventions. When these are insufficient to achieve the desired LDL targets or the TGs remain elevated beyond 150 mg/dL, then the addition of eicosapentaenoic acid ethyl ester or fenofibrate should be considered.[3]

Monitoring of lipids and enzymes for patients on lipid-lowering therapy

Lipid-lowering increases the risk of side effects from pharmacological treatment, and the question of how to monitor safety during treatment has become more important [Table 13] and [Table 14]. Monitoring strategies for Statin therapy [Figure 5].{Figure 5}{Table 13}{Table 14}

 Health Technology Assessment Trends on Dyslipidemia Treatments

Health-care system and access to care in Saudi Arabia

Saudi Arabia is one of the largest Arab nations in the Middle East region with a population that has been rapidly growing over years, as established by the Saudi census. This rise is the main reason for increasing demands on all aspects of health care. Just like many other countries, Saudi Arabia is struggling to provide quality health-care services to its citizens, and this imposes big efforts to be devoted to controlling their costs while at the same time ensuring the quality of care. Healthcare spending in the kingdom is led mainly by governmental expenditure through the MOH and augmented by other governmental organizations ((ex. the military health services), together with a reasonable contribution from the private sector which is consistently increasing.[137],[138] Notwithstanding that there are several methodical and structured health-care institutions, this also hinders efficient coordination and engenders inefficient allocation of resources.[139]

In line with this Saudi landscape, the released Health Sector Transformation Program-Vision 2030 advocates the principle of value-based care and has assigned definite initiatives that focus on including health economics to improve access to all health services through optimal coverage and comprehensive and equitable geographical distribution.[140]

Economic burden of cardiovascular diseases in Saudi Arabia and health technology assessment overview

In Saudi Arabia, CVD imposes a massive economic burden along with enormous resource utilization. For each patient with CVD, the direct medical costs per event were estimated to be $US10,710 in 2011.[15] Moreover, CVD accounts for 41,000 deaths (45.7% of all deaths) every year in Saudi Arabia.[141] A budget impact analysis for the use of PCSK9 monoclonal antibodies in combination with statins for the treatment of uncontrolled LDL-C in CHD or hypercholesterolemia patients in Saudi Arabia was published in 2020. The aim was to evaluate the budgetary impact of introducing PCSK9 monoclonal antibodies as an add-on to statin therapy for the management of uncontrolled LDL-C levels among patients with CHD in the Saudi MOH over 5 years. The introduction of PCSK9 monoclonal antibodies resulted in an increased cost of SAR 91.16 million (6.1%), where the cost of the drug itself was the major contributor to the total cost. The use of PCSK9 monoclonal antibodies was associated with a gradual decrease in the annual number of CV events (ranging from 0.3% in year 1 to 1.5% in year 5) compared to other PCSK9 monoclonal antibodies-lacking measures. The CV event cost was reduced by 13.55 million (4.5%) with the addition of PCSK9 monoclonal antibodies compared to no PCSK9 monoclonal antibodies over 5 years.[142] Seven published cost-effectiveness analysis studies were conducted based on Saudi settings between 2015 and 2020, which reflect the need to develop a set of social utility values in Saudi Arabia.[143]

As per the WHO definition, health technology assessment (HTA) is “the systematic evaluation of properties, effects, and/or impacts of health technology. It is a multidisciplinary process to evaluate the social, economic, organizational, and ethical issues of a health intervention or health technology. The main purpose of conducting an assessment is to inform policy decision-making.”[144] In Saudi Arabia's pursuit to adopt and deploy the HTA in decision-making processes, especially in those related to reimbursement decision-making on the national level, MOH has started focusing on capacity building and establishing proper infrastructures to bring more efficiency to it and optimize the reimbursement review timelines. Saudi MOH has already initiated two critical projects, which will be a cornerstone for the HTA, including the valuation of the Saudi utilities and establishing a cost-effectiveness threshold.

Given the multiple HTA agencies worldwide and the fact that the decision-making process differs between countries whose decision-making is determined only by clinical inputs, those that are more dependent on economic ones, and those who adopt a hybrid model, it is critical to assess the countries/HTA agencies which could be used as a proper benchmark for Saudi Arabia. For PCSK9 monoclonal antibodies drugs, HTA reviews gained positive recommendations in many countries such as Australia, Poland, Netherlands, Spain, Croatia, and others, or positive recommendations with restrictions in England, China, Scotland, and others. Similarly, inclisiran gained positive recommendations in England or positive recommendations with restrictions in the Netherlands. Recommendations for proper HTA implementation regarding dyslipidemia treatments in Saudi Arabia are presented in [Table 15].{Table 15}

 Gaps in Care and Strategies to Encourage Adoption of Preventive Measures

In addressing hypercholesterolemia, it is critical to identify the challenges facing practitioners in Saudi Arabia. First and foremost, there are no regional data that provide a basis for predictive risk scores, capture population-level CV outcomes, and assess the response of local populations to preventive measures. Second, there is a lack of insight into the burden of ASCVD as well as the application of international guidelines regionally. This is registered both at the level of individual patients and health-care practitioners.[145],[146],[147] Finally, an important impediment to a unified policy has been the fragmented health-care system in Saudi Arabia. With multiple parallel public systems, there are multiple prioritization matrices, redundant care plans, and disjointed medical records. Ultimately, health-care expenditure and comprehensive oversight are difficult to streamline across these systems.[80],[140],[148],[149]

Solutions for this complex challenge require multilevel interventions. Elaboration of national guidelines rises to the forefront by emphasizing the importance of prevention pathways and defining targets for both individual patients and treating health-care workers. [Figure 6] Strategies to encourage the adoption of these guidelines include the following:{Figure 6}

Comprehensive solutions

Establishment of standardized clinical pathways that are shared across all specialties and endorsed by policymakers [Figure 7]Establishment of primary prevention and advanced lipidology clinics that screen and optimize treatment plansEstablishment of a unified medical record that facilitates consistent adoption of preventive therapiesIncrease public awareness through national campaignsProvide infographics through social media that counteract the misinformation.{Figure 7}

Long-term solutions

Generate national data to guide future practices and tailor recommendations to the local populationInvest in lipid training programs to create experts in the fieldDesign national-level programs to monitor the impact of preventive measures on long-term outcomes and cost-efficiencyEngage government agencies such as the Saudi Food and Drug Authority (SFDA) to provide food labeling, and city planning/municipalities to improve parks/sidewalks to enable accessible activities that encourage lifestyle modification and permit exercise and physical activities in safe, dedicated outdoor areas.

 Key Messages

Several studies have shed light on the alarming status of premature ASCVD risk factors in Saudi Arabia. Counseling and comprehensive interventions, including lifestyle interventions, are recommended to reduce the ASCVD risk profiles. The development of a new risk calculator that is optimized for the Saudi population and that includes all important factors underlying CVD is a current gap that needs to be metNonfasting/random lipid sampling can be used for screening purposes. If it is positive, the test should be repeated using fasting sampling to confirm the diagnosis, and the fasting lipid profile should be continued for further monitoring. An alternative approach is to measure the non-HDL-C with the nonfasting sampling since this strategy is a more immediate resource and has a better predictor. Apo-B can be measured directly and accurately and better predicts risk than LDL-C or non-HDL-C. If available, Apo-B analysis can be used as an alternative to LDL-C as the primary measurement for screening, diagnosis, and managementRisk modifiers are additional risk factors or individual information that can modify the calculated risk in ASCVD, particularly if the individual's risk is close to a decision threshold. Risk enhancers are several other factors associated with ASCVD. Assessing for risk-enhancing factors can help guide decisions about preventive interventions in adults at borderline or intermediate risk and to adjust the intensity of LDL-lowering therapyCAC score assessment with CT should be considered in individuals at low or moderate risk in whom the respective LDL-C goal is not achieved with lifestyle intervention aloneAggressive lipid management has been demonstrated to improve CV outcomes in different clinical settings such as ACS and other very high-risk entities, namely FH, diabetes, and CKDEstablishing national programs and policies (i.e. national Saudi FH registry, supporting genetic analyses, setting up of specialized lipid clinics, and raising physician awareness) is recommended for early detection of FH in Saudi Arabia, which is particularly important among high-risk populationsStatins are the first-line drugs for dyslipidemia. If the treatment goal is not achieved with statins, a combination with the other treatment options is recommended. Myopathy has been reported more frequently with fibrates than with statins alonePCSK9 monoclonal antibodies have shown a further reduction in ASCVD risk in patients who are in high or very high CVD risk groups. Furthermore, PCSK9 monoclonal antibodies have proven to significantly reduce LDL-C levels in the aforementioned groups when combined with statins and/or ezetimibeStrengthening the treatment goals is important to ensure that treatment of the highest-risk patients achieves the largest LDL-C reduction possible by setting both a minimum percentage LDL-C reduction (50%) and an absolute LDL-C treatment goal of <1.4 mmol/L (<55 mg/dL) for very high-risk patients and of <1 mmol/L in the extremely high-risk group (recurrence)To appropriately manage hypercholesterolemia in the Saudi population, it is critical to adopt a multidisciplinary approach that involves the patient, physician, medical societies, and government agencies. Strategies to encourage the adoption of these guidelines include comprehensive and long-term solutions.

 Evidence-Based “To Do” and “Not To Do”

The recommended evidence based “to do” and “not to do” in dyslipidemia management are summarized [Table 16].{Table 16}


The authors would like to thank Dr. Radwa Ahmed Batran and Dr. Gehad El Ashal from RAY-CRO, Egypt, for their valuable editorial support. The authors also acknowledge Dr. Omar M. Hussein, Dr. Reham Elgarhy, and Dr. Mosaad I. Morsy from RAY-CRO, Egypt, for their valuable review and guidance.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.


1Aljuaid M, Mannan F, Chaudhry Z, Rawaf S, Majeed A. Quality of care in university hospitals in Saudi Arabia: A systematic review. BMJ Open 2016;6:e008988.
2Almutairi KM, Moussa M. Systematic review of quality of care in Saudi Arabia. A forecast of a high quality health care. Saudi Med J 2014;35:802-9.
3Mach F, Baigent C, Catapano AL, Koskinas KC, Casula M, Badimon L, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: Lipid modification to reduce cardiovascular risk. Eur Heart J 2020;41:111-88.
4Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, Blumenthal RS, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the management of blood cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation 2019;139:e1082-143.
5Ray KK, Reeskamp LF, Laufs U, Banach M, Mach F, Tokgözoğlu LS, et al. Combination lipid-lowering therapy as first-line strategy in very high-risk patients. Eur Heart J 2022;43:830-3.
6World Health Organization. Handbook for Guideline Development. Available from: https://apps.who.int/iris/bitstream/handle/10665/75146/9789241548441_eng.pdf. [Last accessed on 2022 Feb 10].
7Althumiri NA, Basyouni MH, AlMousa N, AlJuwaysim MF, Almubark RA, BinDhim NF, et al. Obesity in Saudi Arabia in 2020: Prevalence, distribution, and its current association with various health conditions. Healthcare (Basel) 2021;9:311.
8Alhabib KF, Batais MA, Almigbal TH, Alshamiri MQ, Altaradi H, Rangarajan S, et al. Demographic, behavioral, and cardiovascular disease risk factors in the Saudi population: Results from the Prospective Urban Rural Epidemiology study (PURE-Saudi). BMC Public Health 2020;20:1213.
9IDF Diabetes Atlas 2021,IDF Diabetes Atlas. Available from: https://diabetesatlas.org/atlas/tenth-edition/. [Last accessed on 2022 Jan 26].
10Saudi Arabia Demographics 2020 (Population, Age, Sex, Trends) – Worldometer. Available from: https://www.worldometers.info/demographics/saudi-arabia-demographics/. [Last accessed on 2022 Jan 26].
11Global Health Estimates: Leading Causes of Death. Available from: https://www.who.int/data/gho/data/themes/mortality-and-global-health-estimates/ghe-leading-causes-of-death. [Last accessed on 2022 Feb 24].
12Tyrovolas S, El Bcheraoui C, Alghnam SA, Alhabib KF, Almadi MA, Al-Raddadi RM, et al. The burden of disease in Saudi Arabia 1990–2017: Results from the Global Burden of Disease Study 2017. Lancet Planet Health 2020;4:e195-208.
13Memish ZA, Jaber S, Mokdad AH, AlMazroa MA, Murray CJ, Al Rabeeah AA, et al. Burden of disease, injuries, and risk factors in the Kingdom of Saudi Arabia, 1990-2010. Prev Chronic Dis 2014;11:E169.
14Alzeidan R, Rabiee F, Mandil A, Hersi A, Fayed A. Non-communicable disease risk factors among employees and their families of a Saudi university: An epidemiological study. PLoS One 2016;11:e0165036.
15Osman AM, Alsultan MS, Al-Mutairi MA. The burden of ischemic heart disease at a major cardiac center in Central Saudi Arabia. Saudi Med J 2011;32:1279-84.
16Alharthi FS, Alrahimi JS, Alotaibi AA, Alhamdi DA, Ibrahim BM, Badeeb YA. Prevalence of undiagnosed cardiovascular risk factors in adults aged 20–40: A cross-sectional study in 2016 in Jeddah, Saudi Arabia. Cardiol Res 2017;8:111-6.
17D'Agostino RB Sr., Vasan RS, Pencina MJ, Wolf PA, Cobain M, Massaro JM, et al. General cardiovascular risk profile for use in primary care: The Framingham Heart Study. Circulation 2008;117:743-53.
18Conroy RM, Pyörälä K, Fitzgerald AP, Sans S, Menotti A, De Backer G, et al. Estimation of ten-year risk of fatal cardiovascular disease in Europe: The SCORE project. Eur Heart J 2003;24:987-1003.
19Hippisley-Cox J, Coupland C, Vinogradova Y, Robson J, Minhas R, Sheikh A, et al. Predicting cardiovascular risk in England and Wales: Prospective derivation and validation of QRISK2. BMJ 2008;336:1475-82.
20Assmann G, Cullen P, Schulte H. Simple scoring scheme for calculating the risk of acute coronary events based on the 10-year follow-up of the prospective cardiovascular Münster (PROCAM) study. Circulation 2002;105:310-5.
21Ridker PM, Buring JE, Rifai N, Cook NR. Development and validation of improved algorithms for the assessment of global cardiovascular risk in women: The Reynolds Risk Score. JAMA 2007;297:611-9.
22Ridker PM, Paynter NP, Rifai N, Gaziano JM, Cook NR. C-reactive protein and parental history improve global cardiovascular risk prediction: The Reynolds Risk Score for men. Circulation 2008;118:2243-51.
23Ferrario M, Chiodini P, Chambless LE, Cesana G, Vanuzzo D, Panico S, et al. Prediction of coronary events in a low incidence population. Assessing accuracy of the CUORE Cohort Study prediction equation. Int J Epidemiol 2005;34:413-21.
24Goff DC Jr., Lloyd-Jones DM, Bennett G, Coady S, D'Agostino RB Sr., Gibbons R, et al. 2013 ACC/AHA guideline on the assessment of cardiovascular risk: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014;63:2935-59.
25Hajifathalian K, Ueda P, Lu Y, Woodward M, Ahmadvand A, Aguilar-Salinas CA, et al. A novel risk score to predict cardiovascular disease risk in national populations (Globorisk): A pooled analysis of prospective cohorts and health examination surveys. Lancet Diabetes Endocrinol 2015;3:339-55.
26Woodward M, Brindle P, Tunstall-Pedoe H, SIGN Group on Risk Estimation. Adding social deprivation and family history to cardiovascular risk assessment: The ASSIGN score from the Scottish Heart Health Extended Cohort (SHHEC). Heart 2007;93:172-6.
27Faeh D, Braun J, Rufibach K, Puhan MA, Marques-Vidal P, Bopp M, et al. Population specific and up to date cardiovascular risk charts can be efficiently obtained with record linkage of routine and observational data. PLoS One 2013;8:e56149.
28Alshamiri M, Ghanaim MM, Barter P, Chang KC, Li JJ, Matawaran BJ, et al. Expert opinion on the applicability of dyslipidemia guidelines in Asia and the Middle East. Int J Gen Med 2018;11:313-22.
29SCORE Risk Charts. Available from: https://www.escardio.org/Education/Practice-Tools/CVD-prevention-toolbox/SCORE-Risk-Charts. [Last accessed on 2022 Feb 10].
30ESC CVD Risk Calculation App. Available from: https://www.escardio.org/Education/ESC-Prevention-of-CVD-Programme/Risk-assessment/esc-cvd-risk-calculation-app. [Last accessed on 2022 Feb 10].
31Authors/Task Force Members, Catapano AL, Graham I, De Backer G, Wiklund O, Chapman MJ, et al. 2016 ESC/EAS Guidelines for the management of dyslipidaemias: The Task Force for the Management of Dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS) Developed with the special contribution of the European Assocciation for Cardiovascular Prevention and Rehabilitation (EACPR). Atherosclerosis 2016;253:281-344.
32Cooney MT, Dudina AL, Graham IM. Value and limitations of existing scores for the assessment of cardiovascular risk: A review for clinicians. J Am Coll Cardiol 2009;54:1209-27.
33AlHabib KF, Hersi A, AlFaleh H, Kurdi M, Arafah M, Youssef M, et al. The Saudi Project for Assessment of Coronary Events (SPACE) registry: Design and results of a phase I pilot study. Can J Cardiol 2009;25:e255-8.
34Alhabib KF, Sulaiman K, Al-Motarreb A, Almahmeed W, Asaad N, Amin H, et al. Baseline characteristics, management practices, and long-term outcomes of Middle Eastern patients in the Second Gulf Registry of Acute Coronary Events (Gulf RACE-2). Ann Saudi Med 2012;32:9-18.
35Arnett DK, Blumenthal RS, Albert MA, Buroker AB, Goldberger ZD, Hahn EJ, et al. 2019 ACC/AHA Guideline on the primary prevention of cardiovascular disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation 2019;140:e596-646.
36Ference BA, Graham I, Tokgozoglu L, Catapano AL. Impact of lipids on cardiovascular health: JACC health promotion series. J Am Coll Cardiol 2018;72:1141-56.
37McCormack T, Dent R, Blagden M. Very low LDL-C levels may safely provide additional clinical cardiovascular benefit: The evidence to date. Int J Clin Pract 2016;70:886-97.
38Giugliano RP, Pedersen TR, Park JG, De Ferrari GM, Gaciong ZA, Ceska R, et al. Clinical efficacy and safety of achieving very low LDL-cholesterol concentrations with the PCSK9 inhibitor evolocumab: A prespecified secondary analysis of the FOURIER trial. Lancet 2017;390:1962-71.
39Karagiannis AD, Mehta A, Dhindsa DS, Virani SS, Orringer CE, Blumenthal RS, et al. How low is safe? The frontier of very low (<30 mg/dL) LDL cholesterol. Eur Heart J 2021;42:2154-69.
40Boekholdt SM, Hovingh GK, Mora S, Arsenault BJ, Amarenco P, Pedersen TR, et al. Very low levels of atherogenic lipoproteins and the risk for cardiovascular events: A meta-analysis of statin trials. J Am Coll Cardiol 2014;64:485-94.
41Visseren FL, Mach F, Smulders YM, Carballo D, Koskinas KC, Bäck M, et al. 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J 2021;42:3227-337.
42Al-Kaabba AF, Al-Hamdan NA, El Tahir A, Abdalla AM, Saeed AA, Hamza MA. Prevalence and correlates of dyslipidemia among adults in Saudi Arabia: Results from a National Survey. Open J Endocr Metab Dis 2012;2:89-97.
43Silverman MG, Ference BA, Im K, Wiviott SD, Giugliano RP, Grundy SM, et al. Association between lowering LDL-C and cardiovascular risk reduction among different therapeutic interventions: A systematic review and meta-analysis. JAMA 2016;316:1289-97.
44Ference BA, Ginsberg HN, Graham I, Ray KK, Packard CJ, Bruckert E, et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel. Eur Heart J 2017;38:2459-72.
45Ahmed AM, Hersi A, Mashhoud W, Arafah MR, Abreu PC, Al Rowaily MA, et al. Cardiovascular risk factors burden in Saudi Arabia: The Africa Middle East Cardiovascular Epidemiological (ACE) study. J Saudi Heart Assoc 2017;29:235-43.
46Al Rasadi K, Almahmeed W, AlHabib KF, Abifadel M, Farhan HA, AlSifri S, et al. Dyslipidaemia in the Middle East: Current status and a call for action. Atherosclerosis 2016;252:182-7.
47Al-Hassan YT, Fabella EL, Estrella E, Aatif M. Prevalence and determinants of dyslipidemia: Data from a Saudi university clinic. Open Public Health J 2018;11:416-24.
48El Bcheraoui C, Memish ZA, Tuffaha M, Daoud F, Robinson M, Jaber S, et al. Hypertension and its associated risk factors in the kingdom of Saudi Arabia, 2013: A national survey. Int J Hypertens 2014;2014:564679.
49Saudi Arabia Diabetes Report 2000–2045. Available from: https://diabetesatlas.org/data/en/country/174/sa.html. [Last accessed on 2022 Mar 20].
50Al Dawish MA, Robert AA, Braham R, Al Hayek AA, Al Saeed A, Ahmed RA, et al. Diabetes mellitus in Saudi Arabia: A review of the recent literature. Curr Diabetes Rev 2016;12:359-68.
51Abuyassin B, Laher I. Diabetes epidemic sweeping the Arab world. World J Diabetes 2016;7:165-74.
52Algabbani AM, Almubark R, Althumiri N, Alqahtani A, BinDhim N. The prevalence of cigarette smoking in Saudi Arabia in 2018. Food Drug Regul Sci J 2018;1:1.
53Alasqah I, Mahmud I, East L, Usher K. A systematic review of the prevalence and risk factors of smoking among Saudi adolescents. Saudi Med J 2019;40:867-78.
54Alsubaie AS. Prevalence and determinants of smoking behavior among male school adolescents in Saudi Arabia. Int J Adolesc Med Health 2018;32: /j/ijamh.2020.32.issue-4/ijamh-2017-0180/ijamh-2017-0180.xml. doi: 10.1515/ijamh-2017-0180. PMID: 29369814.
55Alanazi N. Waterpipe smoking in Saudi Arabia: Action plan. Tob Induc Dis 2019;17:38.
56The 10 Most Obese Countries In The World – WorldAtlas. Available from: https://www.worldatlas.com/articles/29-most-obese-countries-in-the-world.html. [Last accessed on 2021 Nov 27].
57Global Burden of Metabolic Risk Factors for Chronic Diseases Collaboration (BMI Mediated Effects), Lu Y, Hajifathalian K, Ezzati M, Woodward M, Rimm EB, et al. Metabolic mediators of the effects of body-mass index, overweight, and obesity on coronary heart disease and stroke: A pooled analysis of 97 prospective cohorts with 1ƃ8 million participants. Lancet 2014;383:970-83.
58Enani S, Bahijri S, Malibary M, Jambi H, Eldakhakhny B, Al-Ahmadi J, et al. The association between dyslipidemia, dietary habits and other lifestyle indicators among non-diabetic attendees of primary health care centers in Jeddah, Saudi Arabia. Nutrients 2020;12:2441.
59Moradi-Lakeh M, El Bcheraoui C, Afshin A, Daoud F, AlMazroa MA, Al Saeedi M, et al. Diet in Saudi Arabia: Findings from a nationally representative survey. Public Health Nutr 2017;20:1075-81.
60Al-Hazzaa HM. Physical inactivity in Saudi Arabia revisited: A systematic review of inactivity prevalence and perceived barriers to active living. Int J Health Sci (Qassim) 2018;12:50-64.
61Al-Hazzaa HM, Abahussain NA, Al-Sobayel HI, Qahwaji DM, Musaiger AO. Physical activity, sedentary behaviors and dietary habits among Saudi adolescents relative to age, gender and region. Int J Behav Nutr Phys Act 2011;8:140.
62Brauer M, Casadei B, Harrington RA, Kovacs R, Sliwa K, WHF Air Pollution Expert Group. Taking a stand against air pollution – The impact on cardiovascular disease: A joint opinion from the World Heart Federation, American College of Cardiology, American Heart Association, and the European Society of Cardiology. Glob Heart 2021;16:8.
63Rajagopalan S, Al-Kindi SG, Brook RD. Air pollution and cardiovascular disease: JACC state-of-the-art review. J Am Coll Cardiol 2018;72:2054-70.
64Shah AS, Lee KK, McAllister DA, Hunter A, Nair H, Whiteley W, et al. Short term exposure to air pollution and stroke: Systematic review and meta-analysis. BMJ 2015;350:h1295.
65Hystad P, Larkin A, Rangarajan S, AlHabib KF, Avezum Á, Calik KB, et al. Associations of outdoor fine particulate air pollution and cardiovascular disease in 157 436 individuals from 21 high-income, middle-income, and low-income countries (PURE): A prospective cohort study. Lancet Planet Health 2020;4:e235-45.
66Brocato J, Sun H, Shamy M, Kluz T, Alghamdi MA, Khoder MI, et al. Particulate matter from Saudi Arabia induces genes involved in inflammation, metabolic syndrome and atherosclerosis. J Toxicol Environ Health A 2014;77:751-66.
67Langlois MR, Nordestgaard BG, Langsted A, Chapman MJ, Aakre KM, Baum H, et al. Quantifying atherogenic lipoproteins for lipid-lowering strategies: Consensus-based recommendations from EAS and EFLM. Clin Chem Lab Med 2020;58:496-517.
68Cholesterol Treatment Trialists' (CTT) Collaboration, Fulcher J, O'Connell R, Voysey M, Emberson J, Blackwell L, et al. Efficacy and safety of LDL-lowering therapy among men and women: Meta-analysis of individual data from 174,000 participants in 27 randomised trials. Lancet 2015;385:1397-405.
69Navarese EP, Robinson JG, Kowalewski M, Kolodziejczak M, Andreotti F, Bliden K, et al. Association between baseline LDL-C level and total and cardiovascular mortality after LDL-C lowering: A systematic review and meta-analysis. JAMA 2018;319:1566-79.
70Mudd JO, Borlaug BA, Johnston PV, Kral BG, Rouf R, Blumenthal RS, et al. Beyond low-density lipoprotein cholesterol: Defining the role of low-density lipoprotein heterogeneity in coronary artery disease. J Am Coll Cardiol 2007;50:1735-41.
71Emerging Risk Factors Collaboration, Di Angelantonio E, Gao P, Pennells L, Kaptoge S, Caslake M, et al. Lipid-related markers and cardiovascular disease prediction. JAMA 2012;307:2499-506.
72Burgess S, Ference BA, Staley JR, Freitag DF, Mason AM, Nielsen SF, et al. Association of LPA variants with risk of coronary disease and the implications for Lipoprotein (a)-Lowering Therapies: A Mendelian Randomization Analysis. JAMA Cardiol 2018;3:619-27.
73Doran B, Guo Y, Xu J, Weintraub H, Mora S, Maron DJ, et al. Prognostic value of fasting versus nonfasting low-density lipoprotein cholesterol levels on long-term mortality: Insight from the National Health and Nutrition Examination Survey III (NHANES-III). Circulation 2014;130:546-53.
74Cannon CP, Blazing MA, Giugliano RP, McCagg A, White JA, Theroux P, et al. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med 2015;372:2387-97.
75Cholesterol Treatment Trialists' (CTT) Collaboration, Baigent C, Blackwell L, Emberson J, Holland LE, Reith C, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: A meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet 2010;376:1670-81.
76Sabatine MS, Giugliano RP, Keech AC, Honarpour N, Wiviott SD, Murphy SA, et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med 2017;376:1713-22.
77Schwartz GG, Steg PG, Szarek M, Bhatt DL, Bittner VA, Diaz R, et al. Alirocumab and cardiovascular outcomes after acute coronary syndrome. N Engl J Med 2018;379:2097-107.
78Cholesterol Treatment Trialists' (CTT) Collaborators, Mihaylova B, Emberson J, Blackwell L, Keech A, Simes J, et al. The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: Meta-analysis of individual data from 27 randomised trials. Lancet 2012;380:581-90.
79Al-Rubeaan K, Bawazeer N, Al Farsi Y, Youssef AM, Al-Yahya AA, AlQumaidi H, et al. Prevalence of metabolic syndrome in Saudi Arabia – A cross sectional study. BMC Endocr Disord 2018;18:16.
80Alasnag M, Awan Z, Al Ghamdi A, Al Modaimeigh H, Al Shemiri M. Improvement initiative in LDL-C management in Saudi Arabia: A call to action. Int J Cardiol Heart Vasc 2020;31:100667.
81Matsushita K, Jassal SK, Sang Y, Ballew SH, Grams ME, Surapaneni A, et al. Incorporating kidney disease measures into cardiovascular risk prediction: Development and validation in 9 million adults from 72 datasets. EClinicalMedicine 2020;27:100552.
82Gansevoort RT, Correa-Rotter R, Hemmelgarn BR, Jafar TH, Heerspink HJ, Mann JF, et al. Chronic kidney disease and cardiovascular risk: Epidemiology, mechanisms, and prevention. Lancet 2013;382:339-52.
83Alsuwaida AO, Farag YM, Al Sayyari AA, Mousa D, Alhejaili F, Al-Harbi A, et al. Epidemiology of chronic kidney disease in the Kingdom of Saudi Arabia (SEEK-Saudi investigators) – A pilot study. Saudi J Kidney Dis Transpl 2010;21:1066-72.
84LeBlanc ES, Patnode CD, Webber EM, Redmond N, Rushkin M, O'Connor EA. Behavioral and pharmacotherapy weight loss interventions to prevent obesity-related morbidity and mortality in adults: Updated evidence report and systematic review for the US Preventive Services Task Force. JAMA 2018;320:1172-91.
85Mottillo S, Filion KB, Genest J, Joseph L, Pilote L, Poirier P, et al. The metabolic syndrome and cardiovascular risk a systematic review and meta-analysis. J Am Coll Cardiol 2010;56:1113-32.
86Sabatine MS, Morrow DA, Jablonski KA, Rice MM, Warnica JW, Domanski MJ, et al. Prognostic significance of the Centers for Disease Control/American Heart Association high-sensitivity C-reactive protein cut points for cardiovascular and other outcomes in patients with stable coronary artery disease. Circulation 2007;115:1528-36.
87Johri AM, Nambi V, Naqvi TZ, Feinstein SB, Kim ES, Park MM, et al. Recommendations for the assessment of carotid arterial plaque by ultrasound for the characterization of atherosclerosis and evaluation of cardiovascular risk: From the American Society of Echocardiography. J Am Soc Echocardiogr 2020;33:917-33.
88Khaing W, Vallibhakara SA, Attia J, McEvoy M, Thakkinstian A. Effects of education and income on cardiovascular outcomes: A systematic review and meta-analysis. Eur J Prev Cardiol 2017;24:1032-42.
89Schultz WM, Kelli HM, Lisko JC, Varghese T, Shen J, Sandesara P, et al. Socioeconomic status and cardiovascular outcomes: Challenges and interventions. Circulation 2018;137:2166-78.
90Al-Aly Z, Xie Y, Bowe B. High-dimensional characterization of post-acute sequelae of COVID-19. Nature 2021;594:259-64.
91Ayoubkhani D, Khunti K, Nafilyan V, Maddox T, Humberstone B, Diamond I, et al. Post-covid syndrome in individuals admitted to hospital with covid-19: Retrospective cohort study. BMJ 2021;372:n693.
92Huang C, Huang L, Wang Y, Li X, Ren L, Gu X, et al. 6-month consequences of COVID-19 in patients discharged from hospital: A cohort study. Lancet 2021;397:220-32.
93Carfì A, Bernabei R, Landi F, Gemelli Against COVID-19 Post-Acute Care Study Group. Persistent symptoms in patients after acute COVID-19. JAMA 2020;324:603-5.
94Daugherty SE, Guo Y, Heath K, Dasmariñas MC, Jubilo KG, Samranvedhya J, et al. Risk of clinical sequelae after the acute phase of SARS-CoV-2 infection: Retrospective cohort study. BMJ 2021;373:n1098.
95Xie Y, Xu E, Bowe B, Al-Aly Z. Long-term cardiovascular outcomes of COVID-19. Nat Med 2022;28:583-90.
96Thanassoulis G, Williams K, Ye K, Brook R, Couture P, Lawler PR, et al. Relations of change in plasma levels of LDL-C, non-HDL-C and apoB with risk reduction from statin therapy: A meta-analysis of randomized trials. J Am Heart Assoc 2014;3:e000759.
97Szummer K, Wallentin L, Lindhagen L, Alfredsson J, Erlinge D, Held C, et al. Improved outcomes in patients with ST-elevation myocardial infarction during the last 20years are related to implementation of evidence-based treatments: Experiences from the SWEDEHEART registry 1995-2014. Eur Heart J 2017;38:3056-65.
98Schwartz GG, Olsson AG, Ezekowitz MD, Ganz P, Oliver MF, Waters D, et al. Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: The MIRACL study: A randomized controlled trial. JAMA 2001;285:1711-8.
99Ray KK, Cannon CP, McCabe CH, Cairns R, Tonkin AM, Sacks FM, et al. Early and late benefits of high-dose atorvastatin in patients with acute coronary syndromes: Results from the PROVE IT-TIMI 22 trial. J Am Coll Cardiol 2005;46:1405-10.
100Pitt B, Loscalzo J, Ycas J, Raichlen JS. Lipid levels after acute coronary syndromes. J Am Coll Cardiol 2008;51:1440-5.
101Berwanger O, Santucci EV, de Barros E Silva PG, Jesuíno IA, Damiani LP, Barbosa LM, et al. Effect of loading dose of atorvastatin prior to planned percutaneous coronary intervention on major adverse cardiovascular events in acute coronary syndrome: The SECURE-PCI Randomized Clinical Trial. JAMA 2018;319:1331-40.
102De Rosa S, Arcidiacono B, Chiefari E, Brunetti A, Indolfi C, Foti DP. Type 2 diabetes mellitus and cardiovascular disease: Genetic and epigenetic links. Front Endocrinol (Lausanne) 2018;9:2.
103Emerging Risk Factors Collaboration, Sarwar N, Gao P, Seshasai SR, Gobin R, Kaptoge S, et al. Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: A collaborative meta-analysis of 102 prospective studies. Lancet 2010;375:2215-22.
104Donahoe SM, Stewart GC, McCabe CH, Mohanavelu S, Murphy SA, Cannon CP, et al. Diabetes and mortality following acute coronary syndromes. JAMA 2007;298:765-75.
105Kohli P, Waters DD, Nemr R, Arsenault BJ, Messig M, DeMicco DA, et al. Risk of new-onset diabetes and cardiovascular risk reduction from high-dose statin therapy in pre-diabetics and non-pre-diabetics: An analysis from TNT and IDEAL. J Am Coll Cardiol 2015;65:402-4.
106Kohli P, Knowles JW, Sarraju A, Waters DD, Reaven G. Metabolic markers to predict incident diabetes mellitus in statin-treated patients (from the Treating to New Targets and the Stroke Prevention by Aggressive Reduction in Cholesterol Levels Trials). Am J Cardiol 2016;118:1275-81.
107de Carvalho LS, Campos AM, Sposito AC. Proprotein convertase Subtilisin/Kexin type 9 (PCSK9) inhibitors and incident type 2 diabetes: A systematic review and meta-analysis with over 96,000 patient-years. Diabetes Care 2018;41:364-7.
108Chronic Kidney Disease Prognosis Consortium, Matsushita K, van der Velde M, Astor BC, Woodward M, Levey AS, et al. Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: A collaborative meta-analysis. Lancet 2010;375:2073-81.
109Toth PP, Dwyer JP, Cannon CP, Colhoun HM, Rader DJ, Upadhyay A, et al. Efficacy and safety of lipid lowering by alirocumab in chronic kidney disease. Kidney Int 2018;93:1397-408.
110Tuñón J, Steg PG, Bhatt DL, Bittner VA, Díaz R, Goodman SG, et al. Effect of alirocumab on major adverse cardiovascular events according to renal function in patients with a recent acute coronary syndrome: Prespecified analysis from the ODYSSEY OUTCOMES randomized clinical trial. Eur Heart J 2020;41:4114-23.
111Charytan DM, Sabatine MS, Pedersen TR, Im K, Park JG, Pineda AL, et al. Efficacy and safety of evolocumab in chronic kidney disease in the FOURIER Trial. J Am Coll Cardiol 2019;73:2961-70.
112Toth PP, Worthy G, Gandra SR, Sattar N, Bray S, Cheng LI, et al. Systematic review and network meta-analysis on the efficacy of evolocumab and other therapies for the management of lipid levels in hyperlipidemia. J Am Heart Assoc 2017;6:e005367.
113Regitz-Zagrosek V, Roos-Hesselink JW, Bauersachs J, Blomström-Lundqvist C, Cífková R, De Bonis M, et al. 2018 ESC Guidelines for the management of cardiovascular diseases during pregnancy. Eur Heart J 2018;39:3165-241.
114Parikh NI, Gonzalez JM, Anderson CA, Judd SE, Rexrode KM, Hlatky MA, et al. Adverse pregnancy outcomes and cardiovascular disease risk: Unique opportunities for cardiovascular disease prevention in women: A scientific statement from the American Heart Association. Circulation 2021;143:e902-16.
115American College of Obstetricians and Gynecologists' Presidential Task Force on Pregnancy and Heart Disease and Committee on Practice Bulletins-Obstetrics. ACOG practice bulletin no. 212: Pregnancy and heart disease. Obstet Gynecol 2019;133:e320-56.
116Stein R, Ferrari F, Scolari F. Genetics, dyslipidemia, and cardiovascular disease: New insights. Curr Cardiol Rep 2019;21:68.
117Patel RS. The continuing challenge of familial hypercholesterolaemia. Eur Heart J Qual Care Clin Outcomes 2017;3:253-5.
118Alhabib KF, Al-Rasadi K, Almigbal TH, Batais MA, Al-Zakwani I, Al-Allaf FA, et al. Familial hypercholesterolemia in the Arabian Gulf region: Clinical results of the Gulf FH Registry. PLoS One 2021;16:e0251560.
119Hu P, Dharmayat KI, Stevens CA, Sharabiani MT, Jones RS, Watts GF, et al. Prevalence of familial hypercholesterolemia among the general population and patients with atherosclerotic cardiovascular disease: A systematic review and meta-analysis. Circulation 2020;141:1742-59.
120Alhababi D, Zayed H. Spectrum of mutations of familial hypercholesterolemia in the 22 Arab countries. Atherosclerosis 2018;279:62-72.
121Al-Rasadi K, Alhabib KF, Al-Allaf F, Al-Waili K, Al-Zakwani I, AlSarraf A, et al. The Gulf Familial Hypercholesterolemia Registry (Gulf FH): Design, rationale and preliminary results. Curr Vasc Pharmacol 2020;18:57-64.
122Bhatt DL, Steg PG, Miller M, Brinton EA, Jacobson TA, Ketchum SB, et al. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. N Engl J Med 2019;380:11-22.
123Gencer B, Giugliano RP. Management of LDL-cholesterol after an acute coronary syndrome: Key comparisons of the American and European clinical guidelines to the attention of the healthcare providers. Clin Cardiol 2020;43:684-90.
124Staels B, Dallongeville J, Auwerx J, Schoonjans K, Leitersdorf E, Fruchart JC. Mechanism of action of fibrates on lipid and lipoprotein metabolism. Circulation 1998;98:2088-93.
125Tenenbaum A, Fisman EZ. Fibrates are an essential part of modern anti-dyslipidemic arsenal: Spotlight on atherogenic dyslipidemia and residual risk reduction. Cardiovasc Diabetol 2012;11:125.
126Ray KK, Landmesser U, Leiter LA, Kallend D, Dufour R, Karakas M, et al. Inclisiran in patients at high cardiovascular risk with elevated LDL cholesterol. N Engl J Med 2017;376:1430-40.
127Cuchel M, Bloedon LT, Szapary PO, Kolansky DM, Wolfe ML, Sarkis A, et al. Inhibition of microsomal triglyceride transfer protein in familial hypercholesterolemia. N Engl J Med 2007;356:148-56.
128Marrs JC, Anderson SL. Bempedoic acid for the treatment of dyslipidemia. Drugs Context 2020;9:2020-6-5. doi: 10.7573/dic.2020-6-5. PMID: 32922503; PMCID: PMC7449648.
129Rubino J, MacDougall DE, Sterling LR, Hanselman JC, Nicholls SJ. Combination of bempedoic acid, ezetimibe, and atorvastatin in patients with hypercholesterolemia: A randomized clinical trial. Atherosclerosis 2021;320:122-8.
130Tokgozoglu L, Orringer C, Ginsberg HN, Catapano AL. The year in cardiovascular medicine 2021: Dyslipidaemia. Eur Heart J 2022;43:807-17.
131Olpasiran Trials of Cardiovascular Events and LipoproteiN (a) Reduction – DOSE Finding Study – Full Text View. Available from: https://clinicaltrials.gov/ct2/show/NCT04270760. [Last accessed on 2022 Mar 03].
132Savarese G, De Ferrari GM, Rosano GM, Perrone-Filardi P. Safety and efficacy of ezetimibe: A meta-analysis. Int J Cardiol 2015;201:247-52.
133Wiklund O, Pirazzi C, Romeo S. Monitoring of lipids, enzymes, and creatine kinase in patients on lipid-lowering drug therapy. Curr Cardiol Rep 2013;15:397.
134Ballantyne CM, Manku MS, Bays HE, Philip S, Granowitz C, Doyle RT Jr., et al. Icosapent ethyl effects on fatty acid profiles in statin-treated patients with high triglycerides: The Randomized, Placebo-controlled ANCHOR Study. Cardiol Ther 2019;8:79-90.
135Gencer B, Djousse L, Al-Ramady OT, Cook NR, Manson JE, Albert CM. Effect of long-term marine ɷ-3 fatty acids supplementation on the risk of atrial fibrillation in randomized controlled trials of cardiovascular outcomes: A systematic review and meta-analysis. Circulation 2021;144:1981-90.
136McKenney JM, Davidson MH, Jacobson TA, Guyton JR, National Lipid Association Statin Safety Assessment Task Force. Final conclusions and recommendations of the National Lipid Association Statin Safety Assessment Task Force. Am J Cardiol 2006;97:89C-94C.
137Alkhenizan A. The pharmacoeconomic picture in Saudi Arabia. Expert Rev Pharmacoecon Outcomes Res 2014;14:483-90.
138Walston S, Al-Harbi Y, Al-Omar B. The changing face of healthcare in Saudi Arabia. Ann Saudi Med 2008;28:243-50.
139AlRuthia Y, Abdulaziz Bin Aydan N, Sulaiman Alorf N, Asiri Y. How can Saudi Arabia reform its public hospital payment models? A narrative review. Saudi Pharm J 2020;28:1520-5.
140Health Sector Transformation Program – Vision 2030. Available from: https://www.vision2030.gov.sa/v2030/vrps/hstp/. [Last accessed on 2021 Dec 15].
141World Health Organization. Mortality and Global Health Estimates. Available from: https://www.who.int/data/gho/data/themes/mortality-and-global-health-estimates. [Last accessed on 2022 Jan 09].
142Al Jedai A, Al-Mudaiheem H, Al-Zoby A, Hamada AB, Sobhy M, Pathak P, et al. PCV17 budget impact analysis of proprotein convertase Subtilisin/Kexin type 9 inhibitors (PCSK9I) use in combination with statins for treatment of uncontrolled low-density lipoprotein-cholesterol in coronary heart disease in the kingdom of Saudi Arabia. Value Health 2020;23:S92-3.
143Algarni MA, Alqahtani SS, Alshehri AM, Alanazi AS, Alzahrani MS, Alolayan SO, et al. Reporting quality of cost-effectiveness analyses conducted in Saudi Arabia: A systematic review. Value Health Reg Issues 2021;25:99-103.
144Health Product Policy and Standards. Available from: https://www.who.int/teams/health-product-policy-and-standards/assistive-and-medical-technology/medical-devices/assessment. [Last accessed on 2022 Jan 27].
145Yusuf S, Islam S, Chow CK, Rangarajan S, Dagenais G, Diaz R, et al. Use of secondary prevention drugs for cardiovascular disease in the community in high-income, middle-income, and low-income countries (the PURE Study): A prospective epidemiological survey. Lancet 2011;378:1231-43.
146Gehani AA, Al-Hinai AT, Zubaid M, Almahmeed W, Hasani MR, Yusufali AH, et al. Association of risk factors with acute myocardial infarction in Middle Eastern countries: The INTERHEART Middle East study. Eur J Prev Cardiol 2014;21:400-10.
147Arafah M, Al-Hinai AT, Al Mahmeed W, Al-Rasadi K, Al Tamimi O, Al Herz S, et al. Centralized pan-Middle East Survey on the undertreatment of hypercholesterolemia: Results from the CEPHEUS study in Arabian Gulf countries. Angiology 2014;65:919-26.
148Reda A, Almahmeed W, Dobrecky-Mery I, Huang PH, Juarez-Herrera U, Ranjith N, et al. A narrative review and expert panel recommendations on dyslipidaemia management after acute coronary syndrome in countries outside Western Europe and North America. Adv Ther 2020;37:1754-77.
149Basulaiman M, El Bcheraoui C, Tuffaha M, Robinson M, Daoud F, Jaber S, et al. Hypercholesterolemia and its associated risk factors-Kingdom of Saudi Arabia, 2013. Ann Epidemiol 2014;24:801-8.
150Kyu HH, Abate D, Abate KH, Abay SM, Abbafati C, Abbasi N, et al. Global, regional, and national disability-adjusted life-years (DALYs) for 359 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990–2017: A systematic analysis for the Global Burden of Disease Study 2017. Lancet 2018;392:1859-922.
151Ainsworth BE, Haskell WL, Herrmann SD, Meckes N, Bassett DR Jr., Tudor-Locke C, et al. 2011 Compendium of Physical Activities: A second update of codes and MET values. Med Sci Sports Exerc 2011;43:1575-81.
152Ridley K, Ainsworth BE, Olds TS. Development of a compendium of energy expenditures for youth. Int J Behav Nutr Phys Act 2008;5:45.